Extracellular Matrix News Volume 11.16 | Apr 30 2020

TOP STORY

Tumor Microenvironment Remodeling Enables Bypass of Oncogenic KRAS Dependency in Pancreatic Cancer

Researchers explored mechanisms involving the tumor microenvironment as a potential basis for resistance to targeting oncogenic KRAS (KRAS*). Using the inducible KrasG12D p53 null pancreatic ductal adenocarcinoma mouse model, gain-of-function screens of epigenetic regulators identified HDAC5 as the top hit enabling KRAS* independent tumor growth. [Cancer Discov] Abstract

(Ranked by impact factor of the journal)

Atrial Myxomas Arise from Multipotent Cardiac Stem Cells

In vitro, the c-kit^pos/CD45^neg/CD31^neg myxoma cells secreted chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kit^pos/CD45^neg/CD31^neg myxoma cells had stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. [Eur Heart J] Full Article

Tumor Microenvironment-Activatable Fe-Doxorubicin Preloaded Amorphous CaCO₃ Nanoformulation Triggers Ferroptosis in Target Tumor Cells

A nanoplatform was simultaneously modified by dendrimers with metalloproteinase-2–sheddable PEG or targeting ligands, which offered the functional balance between circulation longevity and tumor-specific uptake. [Sci Adv] Full Article

Fibroblast Rejuvenation by Mechanical Reprogramming and Redifferentiation

The authors embedded partially reprogrammed spheroids in collagen-I matrices of varying densities, mimicking different 3D tissue constraints. In response to such matrix constraints, these spheroids regained their fibroblastic properties and sprouted to form 3D connective-tissue networks. [Proc Natl Acad Sci USA] Full Article

Effect of Naive and Cancer-Educated Fibroblasts on Colon Cancer Cell Circadian Growth Rhythm

Investigators studied the effect of fibroblasts on the circadian rhythm of growth and protein expression in colon cancer HCT116 cells and found diminished oscillation in the proliferation of HCT116 cells co-cultured with naive fibroblasts, compared with those co-cultured with tumor-associated fibroblasts (TAFs) or those cultured alone, suggesting that TAFs may have lost or gained factors that regulated circadian phenotypes. [Cell Death Dis] Full Article

Activation of STAT3 Is a Key Event in TLR4 Signaling-Mediated Melanoma Progression

Itratumoral activation of TLR4 increased STAT3 activation in the tumor and promoted tumor growth, angiogenesis, epithelial-mesenchymal transition and the formation of an immunosuppressive tumor microenvironment in mice. [Cell Death Dis] Full Article

Characterization of Doxycycline-Mediated Inhibition of Marfan Syndrome-Associated Aortic Dilation by Multiphoton Microscopy

Researchers assessed the effects of long-term doxycycline treatment on the aortic ultrastructure and skin dermis of marfan syndrome mice through immunohistochemical evaluation and quantification of elastic and collagen content and morphology using multiphoton microscopy. [Sci Rep] Full Article

Multi-Layered Free-Form 3D Cell-printed Tubular Construct with Decellularized Inner and Outer Esophageal Tissue-Derived Bioinks

Investigators developed a extrusion-based 3D printing technique to control the size and the shape of the pore in a single extrusion process, so that the fabricated structure had a higher flexibility than that fabricated in the conventional process. [Sci Rep] Full Article

Fundamentals of Extracellular Matrix Biomaterial Assimilation: Effect of Suture Type on Attachment Strength and Cell Repopulation

An intra-abdominal implant model in rats was used to probe assimilation properties at four weeks and 12 weeks with permanent and degradable suture types as well a combination of suture and biologic attachment. The mechanical strength of the attachment was measured by peel testing and the repopulation by automated cell counting of histologic sections. [Plast Reconstr Surg] Full Article

Microfluidic Synthesis of Injectable Angiogenic Microgels

Scientists report a fast-gelling and angiogenic collagen scaffold interlocked by ultra-long DNA programmed with vascular endothelial growth factor aptamers. The DNA interlocking shortened the collagen gelation time by >30-fold, to 40 s and modulated by the microfluidic flows, but the viscoelasticity, biodegradability, and biochemical properties of native collagen remained unaltered. [Cell Rep Phys Sci] Full Article | Graphical Abstract

Responsive Laminarin-Boronic Acid Self-Healing Hydrogels for Biomedical Applications

β-glucan laminarin was functionalized with phenylboronic acid moieties that imparted chemical reactivity toward diol-containing polymers via boronate esterification. The modification, which involved a two-pot reaction, was successfully confirmed by nuclear magnetic resonance spectroscopy. [Polymer J] Abstract

Calreticulin is Important for the Development of Renal Fibrosis and Dysfunction in Diabetic Nephropathy

Knockdown of calreticulin by siRNA in a human proximal tubular cell line showed reduced induction of soluble collagen when stimulated by TGF-β or high glucose as compared to control cells, as well as a reduction in fibronectin and collagen IV transcript levels. [Matrix Biol Plus] Full Article

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The Liver Matrisome, Looking beyond Collagens

A deeper understanding of the hepatic matrisome and its response to injury could yield new mechanistic insights into disease progression and regression, as well as potentially identify new biomarkers for both. The authors discuss the current state of knowledge of the hepatic ECM in liver diseases, and new “omic” approaches to study this compartment. [JHEP Reports] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

FDA grants Carmell Therapeutics Expedited Review for CT-101, Bone Healing Accelerant

Carmell Therapeutics announced that the FDA has granted Fast Track designation for the Company’s first product, a bone healing accelerant. The Fast Track designation provides the company benefits in expediting and accelerating the company’s lead program to the goal of a Biologic License Application approval. [Carmell Therapeutics (BusinessWire, Inc.)] Press Release

The Pandemic’s Effects on Recruiting International STEM Trainees

Pandemic-related concerns that have arisen for science trainees-shuttered labs, research and education delays, anxiety-are applicable across the board. But international graduate students and postdocs face a suite of unique challenges that raise uncertainty about recruiting and supporting this critical group of researchers in the future. [The Scientist] Editorial

As COVID-19 Forces Conferences Online, Scientists Discover Upsides of Virtual Format

As the novel coronavirus outbreak shutters businesses and disrupts everyday life for billions around the globe, massive annual conferences and small society meetings alike have moved online. The new format poses numerous technical and organizational challenges, but it also offers opportunities- for reaching wider audiences, reducing the carbon footprint of meeting travel, and improving diversity and equity. [ScienceInsider] Editorial

In light of COVID-19, many conferences are being cancelled or postponed. As such:

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NEW Assistant Professor – Mammalian Synthetic Biology (Eindhoven University of Technology)

Posdoctoral Researcher – Stem Cells and Regenerative Medicine (Cedars-Sinai Regenerative Medicine Institute)

Postdoctoral Researcher – Regenerative Biomedicine (TU Dresden)

PhD Studentship – 3D Bioprinting of Tissues (Uppsala University)

Postdoctoral Researcher – Regenerative Medicine (ShanghaiTech University)

Principle Investigator – Regenerative Medicine (Guangzhou Institutes of Biomedicine and Health)

Faculty Member – Lung ECM Biology (NIH National Institute of Environmental Health Sciences)

Postdoctoral Researcher – ECM Remodeling in Breast Cancer (Institute of Cancer Research)

Researcher – Biomaterials Scientist (Aspect Biosystems)

Research Associate – Oncology (Zymeworks, Inc.)

Research Scientist – Tumor Microenvironment (Systimmune, Inc.)

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